This invention relates generally to a medical device for the treatment of coma and brain injury, more specifically a medical device for adjunct (add-on) treatment of coma and traumatic brain injury by electrical stimulation neuromodulation of a selected nerve or nerve bundle utilizing an implanted lead-receiver and an external stimulator.
Coma is an abnormally deep state of unconsciousness with an absence of voluntary response to stimuli and with varying degrees of reflex activity. It represents the extreme of a graded continuum of impairment of consciousness, at the opposite pole of the spectrum from full alertness and awareness of the environment. It is not a single uniform disorder, but may stem from different causes such as trauma, disease, or their condition, and which may be characterized by different levels of consciousness. There are degrees of coma, but no varieties. Coma differs from both sleep and syncope (temporary suspension of consciousness due to generalized cerebral ischemia). Cerebral oxygen uptake is normal in sleep or actually increases during the rapid eye movement stage, but cerebral oxygen uptake is abnormally reduced in coma. The patient is incapable of sensing or responding adequately to external stimuli or inner needs, shows little or no spontaneous movement apart from respiration, and no evidence whatever of mental activity.
At the deepest state of coma there is no reaction to stimuli of any intensity, and corneal, pupillary, pharyngeal, tendon and plantar reflexes are absent. Respiration is slow and sometimes periodic (Cheyne-Stokes respiration) and cardiovascular regulating processes may show signs of failure. Lighter degrees of coma (xe2x80x98semicomaxe2x80x99) allow partial response to stimulation, though this is imcomplete, mostly nonpurposive and usually consists of ineffectual movements or rubbing and scratching of the stimulated area. Bladder distension may call forth groaning or ill-coordinated motor stirring but the patient is still incontinent. Tendon refexes may or may not be obtainable, and the plantars may be either flexor or extensor. The Glasgow Coma Scale has proved its usefulness for the grading of depth of coma.
Coma needs to be distinguished from deep sleep and from stupor. In deep sleep and in coma the pictures may be closely similar on superficial observation. But the sleeper can be roused again to normal consciousness by the efforts of the examiner. He may wake spontaneously or unaccustomed stimuli, or in response to inner sensations such as hunger or bladder distension. In sleep there is sporadic continuing mental activity in the form of dreams that leave traces in memory. The distinguishing features usually accepted are that in coma the eyes remain shut even in response to strong arousal stimuli, do not resist passive opening, and do not appear to be watchful or follow moving objects; movements in response to stimulation are never purposeful, and there is no subsequent recall of events or inner fantasies from the time in question.
The Glasgow Coma Scale is now routinely used for acutely head-injured patients. It has proved to be of considerable predictive value in pointing to long-term outcome, in terms of both survival and ultimate levels of disability. The patient""s clinical state is charted regularly on a number of graded parameters: motor responsiveness (no response, extensor response to pain, flexor response, localizing response, obeying commands), verbal performance (nil, without recognizable words, no sustained exchange possible, confused conversation, orientated for person, place and time) an eye opening (nil, in response to pain, in response to speech, spontaneously). Numerical scores are summated for the best responses obtained under each category at a defined point in time. In this way useful predictions can be made, often with 24 hours of injury and more certainly within the first week.
As shown in FIG. 1 recovery from a moderate or severe brain trauma typically involves a progression through a sequence of neurobehavioral syndromes. The initial stage of severely head-injured patients is coma. When consciousness is recovered, a period of delirium and then post-traumatic amnesia is typically seen (stage II). The retrograde component of post-traumatic amnesia is the failure to recall events occurring before the head injury. The anterograde component of post-traumatic amnesia is the failure to store and recall ongoing events occurring since the head injury.
In the system and method of this invention, coma and the residual effects of traumatic brain injury are treated by electrical stimulation neuromodulation of the afferent vagal nerve fibers with an external stimulator with predetermined programs. Since a large percentage of patients with traumatic head injury eventually develop epilepsy which also impedes functional recovery, the anti-epileptic effects of vagus nerve stimulation would also be beneficial.
The vagus nerve 54 provides an easily accessible, peripheral route to modulate central nervous system (CNS) function. Other cranial nerves can be used for the same purpose, but the vagus nerve 54 is preferred because of its easy accessibility. In the human body there are two vagus nerves (VN), the right VN and the left VN. Each vagus nerve is encased in the carotid sheath along with the carotid artery and jugular vein. The innervation of the right and left vagus nerves is different. The innervation of the right vagus nerve is such that stimulating it results in profound bradycardia (slowing of the heart rate). The left vagus nerve has some innervation to the heart, but mostly innervates the visceral organs such as the gastrointestinal tract. It is known that stimulation of the left vagus nerve does not cause any significant deleterious side effects.
One of the fundamental features of the nervous system is its ability to generate and conduct electrical impulses. These can take the form of action potentials, which is defined as a single electrical impulse passing down an axon, and is shown schematically in FIG. 2. The top portion of the figure shows conduction over mylinated axon (fiber) and the bottom portion shows conduction over nonmylinated axon (fiber). These electrical signals will travel along the nerve fibers.
The nerve impulse (or action potential) is an xe2x80x9call or nothingxe2x80x9d phenomenon. That is to say, once the threshold stimulus intensity is reached an action potential 7 will be generated. This is shown schematically in FIG. 3. The bottom portion of the figure shows a train of action potentials.
Most nerves in the human body are composed of thousands of fibers of different sizes. This is shown schematically in FIG. 4. The different sizes of nerve fibers, which carry signals to and from the brain, are designated by groups A, B, and C. The vagus nerve, for example, may have approximately 100,000 fibers of the three different types, each carrying signals. Each axon or fiber of that nerve conducts only in one direction, in normal circumstances.
In a cross section of peripheral nerve it is seen that the diameter of individual fibers vary substantially. The largest nerve fibers are approximately 20 xcexcm in diameter and are heavily myelinated (i.e., have a myelin sheath, constituting a substance largely composed of fat), whereas the smallest nerve fibers are less than 1 xcexcm in diameter and are unmyelinated. As shown in FIG. 5, when the distal part of a nerve is electrically stimulated, a compound action potential is recorded by an electrode located more proximally. A compound action potential contains several peaks or waves of activity that represent the summated response of multiple fibers having similar conduction velocities. The waves in a compound action potential represent different types of nerve fibers that are classified into corresponding functional categories as shown in the table below,
The diameters of group A and group B fibers include the thickness of the myelin sheaths. Group A is further subdivided into alpha, beta, gamma, and delta fibers in decreasing order of size. There is some overlapping of the diameters of the A, B, and C groups because physiological properties, especially in the form of the action potential, are taken into consideration when defining the groups. The smallest fibers (group C) are unmyelinated and have the slowest conduction rate, whereas the myelinated fibers of group B and group A exhibit rates of conduction that progressively increase with diameter.
Compared to unmyelinated fibers, myelinated fibers are typically larger, conduct faster, have very low stimulation thresholds, and exhibit a particular strength-duration curve or respond to a specific pulse width versus amplitude for stimulation. The A and B fibers can be stimulated with relatively narrow pulse widths, from 50 to 200 microseconds (xcexcs), for example. The A fiber conducts slightly faster than the B fiber and has a slightly lower threshold. The C fibers are very small, conduct electrical signals very slowly, and have high stimulation thresholds typically requiring a wider pulse width (300-1,000 xcexcs) and a higher amplitude for activation. Because of their very slow conduction, C fibers would not be highly responsive to rapid stimulation. Selective stimulation of only A and B fibers is readily accomplished. The requirement of a larger and wider pulse to stimulate the C fibers, however, makes selective stimulation of only C fibers, to the exclusion of the A and B fibers, virtually unachievable inasmuch as the large signal will tend to activate the A and B fibers to some extent as well.
The vagus nerve is composed of somatic and visceral afferents and efferents. Usually, nerve stimulation activates signals in both directions (bi-directionally). It is possible however, through the use of special electrodes and waveforms, to selectively stimulate a nerve in one direction only (unidirectionally). The vast majority of vagus nerve fibers are C fibers, and a majority are visceral afferents having cell bodies lying in masses or ganglia in the skull. The central projections terminate largely in the nucleus of the solitary tract, which sends fibers to various regions of the brain (e.g., the thalamus, hypothalamus and amygdala).
Vagus nerve stimulation is a means of directly affecting central function. As shown in FIG. 6, cranial nerves have both afferent pathway 19 (inward conducting nerve fibers which convey impulses toward the brain) and efferent pathway 21 (outward conducting nerve fibers which convey impulses to an effector). The vagus nerve 54 is composed of 80% afferent sensory fibers carrying information to the brain from the head, neck, thorax, and abdomen. The sensory afferent cell bodies of the vagus reside in the nodose ganglion and relay information to the nucleus tractus solitarius (NTS).
FIG. 7 shows the nerve fibers traveling through the spinothalamic tract to the brain. The afferent fibers project primarily to the nucleus of the solitary tract (FIG. 8) which extends throughout the length of the medulla oblangata. A small number of fibers pass directly to the spinal trigeminal nucleus and the reticular formation. As shown schematically in FIG. 8, the nucleus of the solitary tract has widespread projection to cerebral cortex, basal forebrain, thalamus, hypothalamus, amygdala, hippocampus, dorsal raphe, and cerebellum. In summary, neuromodulation of the vagal nerve fibers attempt to cause arousal because of the connections of the nucleus tractus solitarus to the appropriate centers in the brain.
One type of medical device prior art therapy for coma and traumatic brain injury, is generally directed to the use of an implantable lead and an implantable pulse generator technology or xe2x80x9ccardiac pacemaker likexe2x80x9d technology, or stimulation with an implantable Neurocybernetic Prosthesis. In the prior art, the pulse generator is programmed via a xe2x80x9cpersonnel computer (PC)xe2x80x9d based programmer that is adapted with a programmer wand which is placed on top of the skin over the pulse generator implant site, as is shown in FIG. 9. Also in the prior art each parameter is programmed independent of the other parameters. Therefore, millions of different combinations of programs are possible. In the current patent application, approximately nine programs are pre-selected.
U.S. Pat. No. 3,796,221 (Hagfors) is directed to controlling the amplitude, duration and frequency of electrical stimulation applied from an externally located transmitter to an implanted receiver by inductively coupling. Electrical circuitry is schematically illustrated for compensating for the variability in the amplitude of the electrical signal available to the receiver because of the shifting of the relative positions of the transmitter-receiver pair. By highlighting the difficulty of delivering consistent pulses, this patent points away from applications such as the current application, where consistent therapy needs to be continuously sustained over a prolonged period of time. The methodology disclosed is focused on circuitry within the receiver, which would not be sufficient when the transmitting coil and receiving coil assume significantly different orientation, which is likely in the current application. The present invention discloses a novel approach for this problem.
U.S. Pat. Nos. 4,702,254, 4,867,164 and 5,025,807 (Zabara) generally disclose animal research and experimentation related to epilepsy and the like and are directed to stimulating the vagas nerve by using xe2x80x9cpacemaker-likexe2x80x9d technology, such as an implantable pulse generator. The pacemaker technology concept consists of a stimulating lead connected to a pulse generator (containing the circuity and DC power source) implanted subcutaneously or submuscularly, somewhere in the pectoral or axillary region, with an external personal computer (PC) based programmer. Once the pulse generator is programmed for the patient, the fully functional circuity and power source are fully implanted within the patient""s body. In such a system, when the battery is depleted, a surgical procedure is required to disconnect and replace the entire pulse generator (circuitry and power source). These patents neither anticipate practical problems of an inductively coupled system for adjunct therapy of epilepsy, nor suggest solutions to the same for an inductively coupled system for adjunct therapy of partial complex or generalized epilepsy.
U.S. Pat. No. 5,571,150 (Wernicke et al) is generally directed to treatment of coma by electrical nerve stimulation. The methods disclosed in this patent are either acute treatment by positioning an esophageal electrode in the patient, or using an entirely implantable system such as neurocybernetic prostheses for neuromodulation treatment of coma.
U.S. Pat. No. 6,104,956 (Naritoku et al) is generally directed to treating traumatic brain injury by vagus nerve stimulation utilizing an implantable pulse generator (Neurocybernetic Prosthesis).
U.S. Pat. No. 5,304,206 (Baker, Jr. et al) is directed to activation techniques for implanted medical stimulators. The system uses either a magnet to activate the reed switch in the device, or tapping which acts through the piezoelectric sensor mounted on the case of the implanted device, or a combination of magnet and tapping sequence.
U.S. Pat. No. 4,573,481 (Bullara) is directed to an implantable helical electrode assembly configured to fit around a nerve. The individual flexible ribbon electrodes are each partially embedded in a portion of the peripheral surface of a helically formed dielectric support matrix.
U.S. Pat. No. 3,760,812 (Timm et al.) discloses nerve stimulation electrodes that include a pair of parallel spaced apart helically wound conductors maintained in this configuration.
U.S. Pat. No. 4,979,511 (Terry) discloses a flexible, helical electrode structure with an improved connector for attaching the lead wires to the nerve bundle to minimize damage.
Apparatus and method for neuromodulation, in the current application has several advantages over the prior art implantable pulse generator. The external stimulator described here can be manufactured at a fraction of the cost of an implantable pulse generator. The therapy can be freely applied with consideration of battery depletion. Surgical replacement of pulse generator is avoided. The programming is much simpler, and can be adjusted by the patient within certain limits for patient comfort. And, the implanted hardware is significantly less.
The system and method of the current invention also overcomes many of the disadvantages of the prior art by simplifying the implant and taking the programmability into the external stimulator. Further, the programmability of the external stimulator can be controlled remotely, via the wireless medium, as described in a co-pending application. The system and method of this invention uses the patient as his own feedback loop. Once the therapy is prescribed by the physician, the patient can receive the therapy as needed based on symptoms, and the nurse can adjust the stimulation within prescribed limits.
The present invention is directed to system and methods for adjunct (add-on) electrical neuromodulation therapy for coma and traumatic brain injury using an external stimulator with predetermined programs. The system consists of an implantable lead-receiver containing passive circuitry, electrodes adapted for stimulation of the vagus nerve, and a coil for coupling to the external stimulator. The external stimulator contains electronic circuitry to emit electric pulses, power source, primary coil, and predetermined programs. The external primary coil and subcutaneous secondary coil are inductively coupled. The stimulation is according to pre-packaged programs.
In one aspect of the invention the pulse generator contains a limited number -of predetermined programs packaged into the stimulator, which can be accessed directly without a programmer. The limited number of programs can be any number of programs even as many as 100 programs, and such a number is considered within the scope of this invention.
In another feature of the invention, the system provides for proximity sensing means between the primary (external) and secondary (implanted) coils. Utilizing current technology, the physical size of the implantable lead-receiver has become relatively small. However, it is essential that the primary (external) and secondary (implanted) coils be positioned appropriately with respect to each other. The sensor technology incorporated in the present invention aids in the optimal placement of the external coil relative to a previously implanted subcutaneous coil. This is accomplished through a combination of external and implantable or internal components.
In another feature of the invention, the external stimulator has predetermined programs, as well as a manual xe2x80x9cONxe2x80x9d and xe2x80x9cOFFxe2x80x9d button. Each of these programs has a unique combination of pulse amplitude, pulse width, frequency of stimulation, xe2x80x9cONxe2x80x9d time and xe2x80x9cOFFxe2x80x9d time. After the therapy has been initiated by the physician, the patient or caretaker has a certain amount of flexibility for adjusting the therapy (level of stimulation). The patient has the flexibility to decrease (or increase) the level of stimulation (within limits). The manual xe2x80x9cONxe2x80x9d button gives the patient flexibility to immediately start the stimulating pattern at any time. Of the pre-determined programs, patients do not have access to at least one of the programs, and the locked out programs can be activated only by the physician.
Various other features, objects and advantages of the invention will be made apparent from the following description taken together with the drawings.